Probiotics: are they beneficial?

There are wide-ranging probiotic choices in Australasia. We reviewed the efficacy of probiotics for the management of gastrointestinal (GI) conditions in adults and assessed relevance to clinical practice. The benefits of probiotics were inconsistent, with a strong consensus reached for only a few of the indications. As different species/strains and combinations differ in efficacy, results cannot be extrapolated from one to another. This review endorses specific probiotics for limited indications. Efficacy of most marketed probiotic formulations remains unstudied and unproven, warranting further research.

Fecal microbiota transplantation therapy in Crohn's disease: Systematic review.

BACKGROUND: The gastrointestinal microbiota is the key antigenic drive in the inflammatory bowel diseases. Randomized controlled trials (RCTs) in ulcerative colitis have established fecal microbiota transplantation (FMT) as an effective therapy. We have conducted a systematic review to evaluate the efficacy of FMT in Crohn's disease. METHODS: A systematic literature search was performed through to August 2020 (MEDLINE; Embase). Studies were included if they reported FMT administration in patients with Crohn's disease, and reported on clinical outcomes. RESULTS: Fifteen studies published between 2014 and 2020, comprising 13 cohort studies and two RCTs, were included in the analysis. The majority of trials evaluated FMT for induction of remission, with follow-up duration varying from 4 to 52 weeks. One RCT in 21 patients, of single-dose FMT versus placebo, following steroid-induced remission, showed a higher rate of steroid-free clinical remission in the FMT group compared to the control group: 87.5% vs 44.4% at week 10 (P = 0.23). Another RCT, two-dose FMT in 31 patients, showed an overall clinical remission rate of 36% at week 8, however, with no difference in clinical or endoscopic endpoints between FMT administered by gastroscopy and colonoscopy. Considering all studies, the clinical response rates in early follow up were higher following multiple FMT than with single FMT. FMT dose did not appear to influence clinical outcomes, nor did whether FMT was fresh or frozen. FMT delivered via upper gastrointestinal route demonstrated higher early efficacy rates of 75 to 100% compared with lower delivery route rates of 30% to 58%, but on follow up beyond 8 weeks, this difference was not maintained. Whether pre-FMT antibiotic administration was beneficial was not able to be determined due to the limited number of patients receiving antibiotics and varying antibiotic regimens. No serious adverse events were reported. CONCLUSIONS: Preliminary studies suggest that FMT may be an effective therapy in Crohn's disease. However large controlled trials are needed. No serious safety concerns have been identified.

The gut microbiota and gut disease.

The gut microbiota has a key role in the maintenance of good health, and in the pathogenesis of gastrointestinal diseases. These conditions include the inflammatory bowel diseases, colorectal cancer, coeliac disease and metabolic liver disease. Although the nature of the microbial disturbance in these conditions has not been fully characterised, this has not prevented the development of microbially based therapies. Microbial-changing therapies may address newly recognised pathophysiological contributors of disease and have the potential to replace or supplement standard therapies. Antibiotics play a role in initial Clostridiodes difficile disease and some specific inflammatory disorders. Probiotics have a more limited proven role. Faecal microbiota transplantation is of proven therapeutic benefit in recurrent C. difficile disease and ulcerative colitis. We review the current literature for microbiota-targeted therapies in gut disorders.

Long-Term Impact of Direct-Acting Antiviral Agent Therapy in HCV Cirrhosis: Critical Review.

More than 70 million people are chronically infected with hepatitis C virus (HCV) worldwide. Chronic hepatitis C is associated with progressive liver fibrosis, which can result in cirrhosis, liver failure, and hepatocellular carcinoma (HCC). HCV-related liver disease has been the most common indication for liver transplantation in the past decade. The development of direct-acting antiviral agents (DAAs) that are simple, well-tolerated, and highly effective means that most people living with hepatitis C can now be cured, leading the World Health Organization to set targets for reduction in deaths due to viral hepatitis by 2030. In this review, the authors will consider the emerging data showing that curative therapy with DAAs can prevent HCV-related morbidity and mortality, with a focus on patients with HCV-related cirrhosis.

C-reactive protein: an early critical sign of clozapine-related myocarditis.

OBJECTIVE: We present a case of clozapine-related myocarditis, with a rising C-reactive protein as the only initial evidence supporting the diagnosis. METHOD: An otherwise healthy young male presenting with treatment-resistant schizophrenia was started on clozapine. Monitoring was performed. RESULTS: At day 18 he developed fever, tachycardia and a raised C-reactive protein, while troponin levels and echocardiogram remained normal. CONCLUSIONS: Current protocols monitoring for myocarditis have their limitations and can often only be used to support a presumptive diagnosis of myocarditis. In keeping with the current clozapine monitoring guidelines, we demonstrate that a rise in C-reactive protein levels can be a critical early sign of myocarditis warranting close monitoring and serious consideration for cessation of clozapine.

Review article: latent tuberculosis in patients with inflammatory bowel diseases receiving immunosuppression-risks, screening, diagnosis and management.

BACKGROUND: One quarter of the world's population has latent tuberculosis infection (LTBI). Systemic immunosuppression is a risk factor for LTBI reactivation and the development of active tuberculosis. Such reactivation carries a risk of significant morbidity and mortality. Despite the increasing global incidence of inflammatory bowel disease (IBD) and the use of immune-based therapies, current guidelines on the testing and treatment of LTBI in patients with IBD are haphazard with a paucity of evidence. AIM: To review the screening, diagnostic practices and medical management of LTBI in patients with IBD. METHODS: Published literature was reviewed, and recommendations for testing and treatment were synthesised by experts in both infectious diseases and IBD. RESULTS: Screening for LTBI should be performed proactively and includes assessment of risk factors, an interferon-gamma releasing assay or tuberculin skin test and chest X-ray. LTBI treatment in patients with IBD is scenario-dependent, related to geographical endemicity, travel and other factors. Ideally, LTBI therapy should be used prior to immune suppression but can be applied concurrently where urgent IBD medical treatment is required. Management is best directed by a multidisciplinary team involving gastroenterologists, infectious diseases specialists and pharmacists. Ongoing surveillance is recommended during therapy. Newer LTBI therapies show promise, but medication interactions need to be considered. There are major gaps in evidence, particularly with specific newer therapeutic approaches to IBD. CONCLUSIONS: Proactive screening for LTBI is essential in patients with IBD undergoing immune-suppressing therapy and several therapeutic strategies are available. Reporting of real-world experience is essential to refining current management recommendations.

Simple water-based tacrolimus enemas for refractory proctitis.

BACKGROUND AND AIMS: Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal systemic toxicity when administered rectally; we therefore tested a simple tap water-based enema formulation. METHODS: Tacrolimus powder from 1 mg capsules and tap water in a 60 mL syringe were delivered rectally. The primary end-point was endoscopic response (UC: MAYO score reduction by one point; CD: improvement in ulcer number and severity). Secondary end-points included endoscopic remission, clinical response, stool frequency, and rectal bleeding. RESULTS: Seventeen patients [12 UC, five CD, nine female, median age 31 years] with refractory rectal disease were treated. The majority of patients had failed immunosuppressive therapy [88% thiopurine; 71% biologic therapy]. Initial enemas included 1-4 mg tacrolimus daily and 1-3 mg tacrolimus maintenance three times a week for a median of 20 weeks (range 3-204). Concomitant thiopurine or biologic therapy continued. 94% tolerated therapy. Of 12 UC patients, eight (67%) achieved endoscopic remission, one further patient achieved endoscopic response, and median partial MAYO scores decreased (pre:4 vs. post:2; P = 0.010). Of five CD patients, three (60%) achieved endoscopic response, two (40%) endoscopic remission, and three (60%) clinical response. Stool frequency, rectal bleeding, and C-reactive protein levels improved. Strictures became endoscopically passable in all four affected patients. No major adverse events were reported, and four patients had disease flare. CONCLUSIONS: Tacrolimus enemas are easy to prepare, well tolerated, effective, and safe. They should be included in the treatment armamentarium for inflammatory bowel disease-related refractory proctitis.

Idiopathic myointimal hyperplasia of the mesenteric veins: Case report and review of the literature.

In 1991, Genta and Haggitt described four patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins (IMHMV). There are now 33 published cases of IMHMV in the literature; however, this condition is still sufficiently rare that it poses a diagnostic challenge to pathologists and clinicians and is often clinically or histologically confused with inflammatory bowel disease (IBD) or ischemic colitis. IMHMV is characterized by intimal smooth muscle hyperplasia resulting in thickened small and medium-sized mesenteric veins (with arterial sparing). Clinically, it presents with symptoms that mimic IBD, such as bloody diarrhea, abdominal pain, and weight loss. Surgical resection appears to be curative. The present case describes a 63-year-old Vietnamese man with cardiovascular risk factors who was diagnosed with IMHMV after many months of severe symptoms. A review of the current literature follows the case report.

A Comparative Analysis Between Antibiotic- and Nonantibiotic-Associated Delayed Cutaneous Adverse Drug Reactions.

BACKGROUND: The difference in clinical presentation, causality assessments, and outcomes of patients with delayed antibiotic-associated cutaneous adverse drug reactions (AA-cADR) and nonantibiotic-associated (NA)-cADR is ill defined. OBJECTIVE: We examined the etiology of AA-cADR, with regard to the type of antibiotic exposure, allergy labeling, and patient outcomes, in comparison with NA-cADR. METHODS: A retrospective observational inpatient cohort study of cADR was performed from January 2004 to August 2014. Patients were divided into AA-cADR and NA-cADR groups for analysis. cADR was defined as erythema multiforme, fixed drug eruption, acute generalized erythematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), drug-associated linear IgA disease, Stevens-Johnson syndrome, and toxic epidermal necrolysis. RESULTS: Of the 84 patients with cADR, 48% were AA-cADR. Male sex (60% vs 32%, P = .004), median length of stay (14.5 vs 11 days, P = .05), median Charlson comorbidity index (3 vs 1, P = .03), and inpatient mortality (20% vs 5%, P = .04) were higher in AA-cADR compared with NA-cADR. The median drug latency was lower in AA-cADR (6 vs 20 days, P = .001). Sulfonamide antibiotics and glycopeptides were implicated in 20% of AA-cADR. DRESS was more frequently reported in AA-cADR. After cADR diagnosis, further antibiotic therapy was administered in 64% of patients, higher in AA-cADR (75%, 30 of 40) compared with NA-cADR (55%, 24 of 44) (P = .06). Fluoroquinolones (53% vs 21%, P = .02), glycopeptides (vancomycin and teicoplanin; 70% vs 38%, P = .05), and carbapenems (33% vs 13%, P = .11) were used more commonly in AA-cADR. CONCLUSIONS: Antibiotics were the cause of cADR requiring hospital admission in 48% of episodes, and were associated with longer length of stay, higher age-adjusted Charlson comorbidity index, shorter drug latency, and mortality. In AA-cADR, glycopeptide and sulfonamide antibiotic exposure predominated.